Background:
Neuromuscular disorders are a group of heterogeneous conditions affecting the nervous system that controls muscle movements. Charcot-Marie-Tooth syndromes are a class of hereditary neuromuscular disorders affecting the motor and sensory systems. Disruptions to these nerves which control these systems cause progressive muscle weakness, atrophy and sensory loss. Charcot-Marie-Tooth may be inherited in an autosomal dominant, recessive or X-linked manner with an age of onset in between the teens to thirties. This test includes sequencing for the four most clinically significant genes associated with these conditions: PMP22, GJB1, MPZ, and MFN2.
Reasons for Referral:
- Abnormal results in electromyogram and nerve conduction studies.
- Positive family history.
- Carrier testing.
Methodology:
This test has two components:
Component 1: Next generation sequencing will analyze the exons or coding regions of 34 Charcot-Marie-Tooth syndrome genes using Illumina NextSeq 500 technology and preparing samples using hybridization probes to enrich exonic regions. Promoter, intronic, etc. regions are not assessed here but may contain variants that impact gene function.
Component 2: Microarray Analysis – A customized CytoSure “exon-centric” array (Oxford Gene Technology) will be used to detect deletions and duplications. The targeted array has enhanced probes targeted to the exonic regions of the 34 Charcot-Marie-Tooth syndrome. The arrays will be run using Agilent SureScan technology. This array is an ideal complement to the next generation sequencing approach to provide a comprehensive mutation spectrum analysis for Charcot-Marie-Tooth syndrome.
Charcot-Marie-Tooth Syndrome Panel (34 genes): AARS, BSCL2, DCTN1, DNAJB2, DNM2, DYNC1H1, EGR2, FGD4, FIG4, GARS, GDAP1, GJB1, HSPB1, HSPB8, IGHMBP2, KIF1B, LITAF, LMNA, LRSAM1, MED25, MFN2, MPZ, MTMR2, NDRG1, NEFL, PMP22, PRPS1, PRX, RAB7A, SBF2, SH3TC2, SPTLC1, TRPV4, YARS
Specimen Requirements:
Blood: EDTA or ACD (Solution A or B):
- Adult: 5 mL
- Child: 5 mL
- Infant: 2-3 mL
A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES. Please include detailed clinical information, including ethnicity, clinical history, and family history.
Test Performed (Days):
Weekly
Turn Around Time:
8 weeks
Shipment Sensitivity Requirements:
- Package and ship specimen to remain cold, but not frozen.
- Ship via overnight express, using the FedEx priority overnight label provided.
- Contact Client Services for shipping kits and instructions at (855) 535-1522.
References:
- Genetics Home Reference: https://ghr.nlm.nih.gov/condition/charcot-marie-tooth-disease
Additional Info: